Status epilepticus (SE) represents an important neurological problem that is associated with significant mortality and moribundity. Although some epidemiologic information is available on characteristics of individuals in whom SE has occurred, little is known about the specific factors contributing to its risk of occurrence. We have recently shown that genetic factors play an important role in determining SE risk, however, the nature of the specific genetic factors involved remains to be determined. Information collected on the frequency of Se in members of the twin registries maintained by the Department of Human Genetics at Virginia Commonwealth University and among their first degree relatives will provide valuable information pertinent to the factors important in its etiology. The primary objective of the proposed study is to continue an investigation of the role of genetic factors in determining risk for SE. Twin and twin kindred studies provide an efficient means for examining the roles of genetic and environmental influences in the etiology of complex disorders like SE. For this reason, SE-positive twins and conjunction with these twin populations currently contains information on over 39,000 twin pairs and their families. The proposed study will focus upon a validated sample that is estimated to include more than 290 twin pairs and 500 twin kindreds who are positive for a history of SE in addition to two groups of controls, one negative for seizures positive for seizures but negative for SE. We believe that the number of validated SE twin pairs expected is a conservative estimate and that we will be able to validate additional cases in the AARP sample and through incident cases in young twins. Data pertinent to selected demographic variables, type and frequency of seizures, and previous history of epilepsy and related health problems will continue to be collected on SE-affected individuals in addition to information on the occurrence of SE in first degree relatives and used in later analyses. Cases will be validated using medical records. Seizure and epileptic syndrome types will be classified using the International Classifications of Seizures and of Epilepsy and Epileptic Syndromes. The unique structure of the data set to be collected will permit the use of several methodological approaches in evaluating the hypotheses put forth. Standard epidemiological methods will be used to examine the role of specific environmental and demographic variables on the occurrence of SE. Multiplex SE-positive twin kindreds will be 4evaluated using segregation analysis techniques. Logistic regression techniques will be used in more detailed analyses of the importance of genetic and specific environmental factors in the development of SE. This study provides the first opportunity ever available to delineate the specific role of genetic factors in determining the risk for SE.